Toxicon最新文献

{"title":"Lepidium meyenii (Maca) polysaccharides mitigate liver toxicity of aflatoxin B1 through activation of NRF-2/GPX and AhR/STAT3 signaling pathways","authors":"Jing Zhang ,&nbsp;Zhen Peng ,&nbsp;Dong Cheng ,&nbsp;Wenhuan Yao ,&nbsp;Hui Li ,&nbsp;Qi Zhang ,&nbsp;Ruisen Guo ,&nbsp;Kunyan Li ,&nbsp;Longrui Zou ,&nbsp;Jia-Sheng Wang ,&nbsp;Qiang Jia ,&nbsp;Tianliang Zhang ,&nbsp;Jun Zhou","doi":"10.1016/j.toxicon.2024.108117","DOIUrl":"10.1016/j.toxicon.2024.108117","url":null,"abstract":"<div><div>Aflatoxin B₁ (AFB₁) can induce serious liver toxicity in human. While completely avoiding AFB₁ exposure is difficult, dietary intake of natural products may be leveraged to mitigate its adverse health effects. The roots of <em>Lepidium meyenii</em> (Maca) is rich in beneficial polysaccharides. Here we first evaluated dietary safety of MPs and then investigated MPs mitigating effects on the liver toxicity of AFB₁. A 28-day sub-acute administration of Maca polysaccharides (MPs) demonstrated to be safe in mice at dose 0.2–1.2 g/kg.bw/day that significantly elevated mice stamina. Also, no toxicity was observed in human PC12 cells treated with MPs 25–100 μg/mL which successfully alleviated cobalt-caused cell apoptosis by ∼20%. In terms of anti-AFB₁ hepatoxicity function, MPs 0.4–1.6 g/kg.bw/day significantly alleviated liver tissue damage, lipid accumulation, ROS damage, NF-κB p65, secretion of cytokines such as IL-6 and TNF-α in AFB₁-treated mice. Flow cytometry found that MPs treatment recovered the elevation of F4/80 in the primary macrophages of AFB₁-treated mice. At molecular level, MPs treatment activated liver NRF-2/GPX/SOD anti-oxidant system. In human macrophage model, MPs restored the inflammatory AhR/STAT3 pathway and mRNA expressions of Tnf-a, Inos, Arg-1 disrupted by AFB₁. Our findings not only add to the current understanding on the toxicity mechanism of AFB₁, but also provide references to the development of dietary intervention strategy using MPs.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108117"},"PeriodicalIF":2.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aflatoxin B1 downregulates ARID3 genes to overcome senescence for inducing hepatocellular carcinoma","authors":"Dilkash Ara,&nbsp;Srinivas Dheeravath,&nbsp;Sathish Kumar Mungamuri","doi":"10.1016/j.toxicon.2024.108114","DOIUrl":"10.1016/j.toxicon.2024.108114","url":null,"abstract":"<div><div>Aflatoxins are major food contaminants, which cause hepatotoxicity, eventually leading to Hepatocellular carcinoma. Activated AFB1 forms adducts with DNA, which in turn activates checkpoint control. We show that AFB1 activates PI3K-Akt signaling, which is critical for cell survival. Simultaneous activation of both DNA checkpoint and proliferative signaling leads to Oncogene-Induced Senescence, a major tumorigenesis barrier. AFB1 downregulates ARID3A and ARID3B proteins to overcome this senescence program to induce hepatic tumors.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108114"},"PeriodicalIF":2.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on Translational toxicology of Senna obtusifolia aqueous extract","authors":"Xin Guo ,&nbsp;Liping Gong ,&nbsp;Chong Guo ,&nbsp;Taotao Cai ,&nbsp;Nana Huang ,&nbsp;Xianhui Shen ,&nbsp;Lisong Sheng ,&nbsp;Rongrong Li ,&nbsp;Yanqing Wang ,&nbsp;Xinmei Zhao ,&nbsp;Wenhe Guo ,&nbsp;Rong Sun","doi":"10.1016/j.toxicon.2024.108113","DOIUrl":"10.1016/j.toxicon.2024.108113","url":null,"abstract":"<div><div>In recent years, the clinical adverse drug reactions (ADR) reports of <em>Senna obtusifolia</em> have been constantly emerging, especially hepatotoxicity. However, it is unclear whether the liver is the only or main toxic target organ. In this study, we conducted a repeated administration experiment with the <em>Senna obtusifolia</em> Aqueous Extract (SE) and PCA analysis was used to determine the primary toxic target organs. The results revealed that the liver was the main toxic target organ and we also verifid the hepatotoxicity in vitro. The mechanism of hepatotoxicity was predicted by network toxicology technology, which was verified by ELISA, qPCR, western blotting and other methods.The results showed that SE could increase the serum levels of TNF-α, IL-6, IL-1β, the mRNA expression levels of ACT1, TRAF6, NF-κB P65 and the protein expression levels of TRAF6, NF-κB P65, P-P65 in rat livers and HepG2 cells, which indicated that SE induced hepatotoxicity might be related to inflammatory response.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108113"},"PeriodicalIF":2.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the drivers of Bothrops snakebite incidence across Brazil: A Spatial Analysis","authors":"Franciely Fernanda Barbosa da Silva ,&nbsp;Thais de Andrade Moura ,&nbsp;Tuany Siqueira-Silva ,&nbsp;José María Gutiérrez ,&nbsp;Pablo Ariel Martinez","doi":"10.1016/j.toxicon.2024.108107","DOIUrl":"10.1016/j.toxicon.2024.108107","url":null,"abstract":"<div><div>Snakebite envenoming poses a significant public health challenge on a global basis, affecting millions of people annually and leading to complications that may result in fatalities. Brazil stands as one of the countries most impacted by snakebite envenoming, with snakes of the <em>Bothrops</em> genus being responsible for most bites. The current study aimed to identify the determinants of <em>Bothrops</em> snakebite incidence across different regions of Brazil. An ecological study was conducted using municipality-aggregated data, with snakebite incidence as the dependent variable. The study period comprised the years 2015–2021. We constructed Species Distribution Models (SDMs) for <em>Bothrops</em> species, and information was collected on precipitation, runoff, maximum and minimum temperatures, native forest, historical forest loss, agriculture, and pasture in each Brazilian municipality. These data were employed to assess the association between snakebite incidence and biotic, climatic, and landscape factors. The data were analyzed using Generalized Least Squares (GLS) regression. The SDMs demonstrated good performance. The average annual snakebite incidence during the study period ranged from zero to 428.89 per 100,000 inhabitants, depending on the municipality. Higher incidence rates were concentrated primarily in municipalities in the northern region of the country. In this study, we found that nationwide, areas with extensive native forests and those that have historically experienced significant loss of forest cover exhibited higher snakebite incidence rates. Additionally, areas with higher temperatures and precipitation levels, as well as greater climatic suitability for the species <em>B. jararaca</em>, showed significantly higher snakebite incidence rates in the South and Southeast of Brazil, respectively. These associations may be linked to increased snake abundance and active behavior, as well as to engagement in activities favoring human-snake contact in these areas. The findings of this study can contribute to the improvement of prevention and control strategies for this public health issue in Brazil.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108107"},"PeriodicalIF":2.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine-learning based prediction model for acute kidney injury induced by multiple wasp stings","authors":"Wen Wu ,&nbsp;Yupei Zhang ,&nbsp;Yilan Zhang ,&nbsp;Xingguang Qu ,&nbsp;Zhaohui Zhang ,&nbsp;Rong Zhang","doi":"10.1016/j.toxicon.2024.108112","DOIUrl":"10.1016/j.toxicon.2024.108112","url":null,"abstract":"<div><div>Acute kidney injury (AKI) following multiple wasp stings is a severe complication with potentially poor outcomes. Despite extensive research on AKI's risk factors, predictive models for wasp sting-related AKI are limited. This study aims to develop and validate a machine learning-based clinical prediction model for AKI in individuals with wasp stings. In this retrospective cohort study, conducted at a tertiary teaching hospital in Yichang, China, from July 2013 to April 2023, 214 patients with wasp sting injuries were analyzed. Using least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression, prognostic variables for AKI were identified. A nomogram incorporating these four variables was constructed. The model's performance was assessed through internal validation, leave-one-out cross-validation, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Among 214 patients affected by wasp stings, 34.6% (74/214) developed AKI. Following LASSO regression and multivariate logistic regression, the number of stings, presence of gross hematuria, systemic inflammatory response index (SIRI), and platelet count were identified as prognostic factors. A nomogram was constructed and evaluated for its predictive accuracy, showing an area under the curve (AUC) of 0.757 (95% CI 0.711 to 0.804) and a concordance index (C-index) of 0.75. Validation confirmed the model's reliability and superior discrimination ability over existing models, as demonstrated by NRI, IDI, and DCA. The developed nomogram effectively predicts AKI risk in wasp sting patients, facilitating early identification and management of those at risk.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108112"},"PeriodicalIF":2.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of Western Gaboon viper (Bitis rhinoceros) envenomation: Successful treatment with South African Institute for Medical Research (SAIMR) antivenom after North American crotalid antivenom failure","authors":"Hannah St. Francis ,&nbsp;Raizada A. Vaid ,&nbsp;Roger Rothenberg ,&nbsp;Robert S. Hoffman ,&nbsp;Sarah G. Mahonski ,&nbsp;Vincent J. Calleo ,&nbsp;Rana Biary ,&nbsp;Capwell E. Taylor ,&nbsp;Joshua Z. Silverberg","doi":"10.1016/j.toxicon.2024.108108","DOIUrl":"10.1016/j.toxicon.2024.108108","url":null,"abstract":"<div><div>We report a case of Western Gaboon viper (<em>Bitis rhinoceros</em>) envenomation in which the patient's symptoms progressed despite treatment with North American crotalid antivenom but improved after receiving South African Institute for Medical Research (SAIMR) polyvalent antivenom.</div><div>A 59-year-old man was hospitalized after reportedly being bitten by a Gaboon viper <em>(Bitis gabonica).</em> On arrival, he had normal vital signs, two puncture wounds on his left hand, and edema distal to the wrist. The hospital contacted the local poison center who conveyed that crotalid antivenom would be ineffective and recommended transfer to a snakebite center for species-appropriate antivenom. However, this recommendation was disregarded. Initial laboratory tests 2 hours after envenomation revealed a platelet count of 77 x 10⁹/L; other parameters were normal. He received six vials of crotalid antivenom (CroFab®) followed by three maintenance doses (total 12 vials). The next morning, swelling had progressed proximal to the elbow and platelets decreased to 37 x 10⁹/L. He was subsequently transferred and received SAIMR polyvalent antivenom. Six hours later, his platelets were 130 x 10⁹/L. The next morning, his swelling had significantly improved. He was discharged the following day. After discharge, it was discovered that the snake was a <em>Bitis rhinoceros</em>.</div><div><em>Bitis gabonica</em> and <em>Bitis rhinoceros</em> are popular captive snakes in the United States. <em>Bitis rhinoceros</em> was formerly a sub-species of <em>B. gabonica</em>, and they are often referred to interchangeably. Their venoms cause tissue edema, coagulopathy, and in severe cases, hemorrhage, dysrhythmias, and death. Antivenom is not widely available in the United States often necessitating patient transfer or antivenom delivery. This case addresses the question of whether crotalid antivenom, which is ubiquitous in the United States, can treat <em>B. gabonica</em> and <em>B. rhinoceros</em> envenomations and highlights the need for consultation with a poison center to facilitate administration of species-appropriate antivenom.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108108"},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of protein profiles in skin secretions of some Rana species: Preliminary insights into antimicrobial activity","authors":"Ebru Tanrıverdi O,&nbsp;Dinçer Ayaz,&nbsp;Yiğit Terzi","doi":"10.1016/j.toxicon.2024.108110","DOIUrl":"10.1016/j.toxicon.2024.108110","url":null,"abstract":"<div><div>Protein profiles of skin secretions of <em>Rana dalmatina</em> (Agile Frog), <em>Rana macrocnemis</em> (Uludağ Frog), <em>Rana tavasensis</em> (Tavas Frog) and <em>Rana holtzi</em> (Taurus Frog) frog species belonging to the <em>Rana</em> genus distributed in the Anatolian region of Türkiye were determined for the first time using the Tricine-SDS-PAGE Electrophoresis method and Coomassie Brilliant Blue (CBB) staining. By the results, some peptides with mass ≤5 kDa were detected. Just one peptide with mass ≤5 kDa was found in the secretion of each <em>R. dalmatina</em>, <em>R. macrocnemis</em>, and <em>R. tavasensis</em> while there was two in <em>R. holtzi</em> secretion. The antibacterial activity of secretions was determined using plate well diffusion assay on <em>E. coli</em>, <em>S. typhimurium</em>, <em>S. aureus</em>, <em>B. cereus</em> and <em>L. monocytogenes</em> bacteria. <em>R. dalmatina</em> created the inhibition zone for <em>S. typhimurium, S. aureus, B. cereus,</em> and <em>L. monocytogenes.</em> The zones of inhibition by <em>R. tavasensis</em> and <em>R. macrocnemis</em> species secretions were observed on <em>S. aureus</em>, <em>B. cereus</em>, and <em>L. monocytogenes</em>. It was found that <em>R. holtzi</em> creates an inhibition zone only on <em>B. cereus.</em> The results showed that the secretion of none of the species doesn't have antibacterial activity on <em>E. coli</em>. The skin secretion of <em>R. dalmatina</em> showed the most activity against bacteria, while <em>R. holtzi</em> had the least.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108110"},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An alternative method for comparing hemorrhagic activity of snake venoms following one of the 3R's principles","authors":"Lídia Jorge Tasima ,&nbsp;Victor Koiti Kavazoi ,&nbsp;Eduardo Oliveira Venancio de Lima ,&nbsp;Kathleen Fernandes Grego ,&nbsp;Anita Mitico Tanaka-Azevedo","doi":"10.1016/j.toxicon.2024.108111","DOIUrl":"10.1016/j.toxicon.2024.108111","url":null,"abstract":"<div><div>Venom-induced hemorrhage analysis usually is performed by Minimum Hemorrhagic Dose (MHD), however a similar method can be used to compare venoms with fewer laboratory animals. Our work compared the MHD of five different venoms, with the size of hemorrhagic spot, finding good correlations in the results. Considering the 3Rs principle, we propose the use of the hemorrhagic spot method to compare hemorrhagic activity of snake venoms, rather than using the MHD method, since the first one needs 5 times less animals than the other.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108111"},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution mapping of deadly scorpions in Iran","authors":"Masoumeh Bardaran ,&nbsp;Sedigheh Mohajer ,&nbsp;Seyed Mahdi Kazemi","doi":"10.1016/j.toxicon.2024.108109","DOIUrl":"10.1016/j.toxicon.2024.108109","url":null,"abstract":"<div><div>Scorpion sting is a problem all over the world and becomes an acute problem when it is associated with death. Iran is known as a region with a large number of scorpions and, of course, with many cases of scorpion stings per year. So far, 11 scorpion species in Iran have been identified as dangerous, of which there are only three species for which deaths have been reported. Due to the importance of these three species, we prepared a distribution map of these three types of scorpions and discuss the implications of these findings in the larger context of dangerous scorpion stings in Iran.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108109"},"PeriodicalIF":2.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial infarction during treatment of Crotalinae envenomation: A case report","authors":"Jacob Robishaw-Denton ,&nbsp;Jennifer Ramirez ,&nbsp;Alisia Bahadir ,&nbsp;Geoffrey Smelski","doi":"10.1016/j.toxicon.2024.108105","DOIUrl":"10.1016/j.toxicon.2024.108105","url":null,"abstract":"<div><div>While myocardial infarction is a rare, but known, potential side effect of snakebite envenomation, snake antivenom has thus far not been associated with any cardiovascular adverse events. We report the case of a 71-year-old man who developed an anterolateral MI during administration of Crotalidae immune F(ab')2 (equine) (ANAVIP), given as treatment for Crotalidae envenomation. The patient required cardiac catheterization with stenting of the left anterior descending artery and was discharged two days later on long-term clopidogrel and aspirin. Treatment of MI in the setting of envenomation should mirror typical management, with consideration of additional antivenom if the ischemia is determined to be venom-induced. Clinicians should have a high index of suspicion for patients with chest pain after snake envenomation or administration of antivenom.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"250 ","pages":"Article 108105"},"PeriodicalIF":2.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}